The association of environmental factors with neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia (ALL).

PURPOSE: To investigate the association of environmental factors, rehabilitation services during therapy and socioeconomic status (SES - insurance type), with neurocognitive outcomes at the end of therapy for survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Survivors (n = 236) treated on the St. Jude Total Therapy Study 16 completed end of therapy testing with performance measures (IQ, attention, processing speed, fine motor skills, academics) and caregiver ratings (attention, executive function, adaptive skills). Environmental factors were abstracted from the medical record. RESULTS: Distribution of sex (47.3% female, p = 0.399), treatment arm (45.5% low risk, 54.5% standard/high risk p = 0.929), insurance type (47.7% private, 52.3% public/none, p = 0.117), and mean age at diagnosis (7.7 vs. 6.8 years, p = 0.143) were similar for groups with (n = 110; 46.6%) and without (n = 126; 53.6%) rehabilitation services during therapy. Compared to those without rehabilitation, the rehabilitation group (n = 110; 46.4%) had more caregiver reported problems with attention (Z = -0.28 vs. 0.43, p = 0.022), executive function (Z = -0.50 vs. -0.08, p = 0.003), and adaptive skills (Z = -0.41 vs.-0.13, p = 0.031). Among the rehabilitation group, there was no difference in outcomes by insurance status. Among those without rehabilitation, those with public insurance had worse neurocognitive outcomes than those with private insurance in IQ (Z = -0.04 vs. -0.45, p = 0.0115), processing speed (Z = -0.10 vs. -0.75, p = 0.0030), reading (Z = 0.18 vs. -0.59, p < 0.0001), and math (Z = -0.04 vs. -0.50, p = 0.0021). CONCLUSION: Participation in rehabilitation services during early intensive therapy is associated with end of therapy caregiver-reported neurocognitive outcomes in daily life.

Selection of colour of sticky trap for monitoring adult bean thrips, Caliothrips fasciatus (Thysanoptera: Thripidae).

Adult bean thrips, Caliothrips fasciatus (Pergande), overwintering inside the navel of navel oranges shipped from California to Australia, are an actionable pest for the importing country, i.e. infested lots are fumigated with methyl bromide. Strict quarantine regulations regarding C. fasciatus prompted studies on the best colour sticky trap that might be used to monitor for bean thrips populations in the vicinity of California citrus groves prior to harvesting fruit for export. Preliminary experiments identified the most attractive trap of each of four colours (blue, green, white, yellow) commonly used to sample adult Thysanoptera. Three trials of a field study were conducted, comparing C. fasciatus capture on the best card of each colour using asparagus ferns naturally infested with high levels of this pest. Based on significantly higher catch on green sticky cards, this colour trap is recommended for potential use in California's bean thrips mitigation plan designed to reduce thrips levels on citrus exported to Australia.

A "weight-listing" paradox for candidates of renal transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.

Ultrasound is now better than mammography for the detection of invasive breast cancer.

OBJECTIVE: This study investigated the use of ultrasound (US) as a first-line diagnostic tool. METHODS: All women attending our breast center underwent bilateral whole-breast US in addition to all other investigations, and results were documented prospectively and preoperatively. RESULTS: Of 796 patients with breast cancer, US was positive in 710 (89%) and mammography in 706 (89%) (P = not significant). Either US or mammogram was positive in 770 (97%). Of 537 (67%) symptomatic patients, US was positive in 497 (93%) and mammography in 465 (87%). Either US or mammography was positive in 515 (96%). Of 259 (33%) screening patients, 220 (85%) had invasive cancer. US was positive in 195 (89%) and mammography in 203 (92%) (P = not significant). Either US or mammography was positive in 217 (99%). Of 39 screening patients with ductal carcinoma in situ (5% of all patients), US was positive in 18 (46%) and mammography in 38 (97%). CONCLUSIONS: US is significantly better than mammography for detecting invasive breast cancer (92% patients). The combination of US and mammography is significantly better than either modality used alone, together resulting in 9% more breast cancers detected.

The universal, situational, and personal needs of cancer patients and their main carers.

The importance of psychosocial factors in the cancer journey for both patients and their carers has been recognised in UK health policy. The aim of this paper is to consider--(1) which needs are regarded as important by patients and their carers; (2) which are the unmet needs of patients and their carers. The study focuses on the responses of 233 paired cancer patients and their carers derived from a cross-sectional questionnaire survey in three health authorities in North West England. The majority of patient-carer pairs expressed the importance of having good relationships with health-care professionals and receiving good-quality information. These can be identified as "universal" needs. A minority of patient-carer pairs expressed the importance of other kinds of needs. These items were mainly to do with managing daily life, emotions, and social identity and can be identified as "situational" or "personal" needs. Where there were discrepancies between patients and carers, patients were likely to identify more needs as important. In contrast, carers have more unmet needs, reflecting their comparative neglect. Broadly, "universal" needs are being met, but "situational" and "personal" needs, particularly among carers, are relatively unmet and require greater attention on the part of nurses and primary care professionals.

Psychosocial needs in cancer patients related to religious belief.

In a study of psychosocial needs amongst cancer patients, the possession of a religious faith has been identified as a significant factor in determining a range of psychosocial needs. Of the 354 respondents to a questionnaire, which included a comprehensive psychosocial needs inventory, 83% said they had a religious faith, and in general these patients were less reliant on health professionals, had less need for information, attached less importance to the maintenance of independence and had less need for help with feelings of guilt, with their sexuality or with some practical matters than those who said they had no religious faith. In addition, they had fewer unmet needs overall (32% compared with 52%). The knowledge of a patient's spirituality should help service providers to predict aspects of psychosocial need and to respond sensitively and appropriately to a patient's experience of cancer.

Cancer and faith. Having faith--does it make a difference among patients and their informal carers?

This research considers the impact of having a religious faith on the cancer experience of patients and informal carers, focusing primarily on the association between faith and psychosocial needs. A questionnaire survey of 1000 patients in the north-west of England returned 402 completed questionnaires; around two-thirds of patients indicated they had an informal carer. Using logistic regression analysis, we examine the relationship between the importance of 48 needs and faith for 189 paired patients and carers, while controlling for the effect of eight socio-demographic and clinical variables. Patients with expressed faith identified fewer psychosocial needs than those without faith. In contrast, carers with expressed faith identified more needs than those without faith in relation to support from family and neighbours. Carers also needed more help with finding a sense of purpose and meaning, and help in dealing with unpredictability. Not surprisingly, both patients and carers with faith identified a greater need for opportunities for personal prayer, support from people of their own faith and support from a spiritual adviser. Various explanations of these differences between patients and carers are proposed. The crucial point is that one should not too readily assume that the cancer experience is shared in the same way by patients and carers. In understanding the faith dimension, one needs to consider both the spiritual and secular aspects of having a religious faith.

Primary care physicians attitude toward diagnosis and treatment of late-life depression.

Underdiagnosis and undertreatment of late-life depression is common, especially in primary care settings. To help assess whether physicians attitude and confidence in diagnosing and managing depression serve as barriers to care, a total of 176 physicians employed in 18 primary care groups were administered surveys to assess attitudes towards diagnosis, treatment, and management of depression in elderly patients, (individuals over 65 years of age). Logistic regression was performed to assess the association of physician characteristics on attitudes. Nearly all of the physicians surveyed felt that depression in the elderly was a primary care problem, and 41% reported late-life depression as the most common problem seen in older patients. Physicians were confident in their ability to diagnose and manage depression, yet 45% had no medical education on depression in the previous three years. Physicians confidence in their ability to diagnose, treat, and manage depression, and their reported adequacy of training, do not appear to correspond to the amount of continuing medical education in depression, suggesting that physician overconfidence may potentially be serving as a barrier to care.

The effect of patient and visit characteristics on diagnosis of depression in primary care.

OBJECTIVES: The purpose of our study was to determine if factors other than the patient' clinical presentation were associated with the likelihood of depression being recognized during a physician office visit. STUDY DESIGN: We used a cross-sectional design. POPULATION: Data from the 1997 and 1998 National Ambulatory Medical Care Surveys were examined. OUTCOMES MEASURED: We assessed the association of factors such as age, sex, race, physician specialty, type of insurance, and visit duration with a recorded depression diagnosis during office visits to primary care physicians. RESULTS: After controlling for symptom presentation, primary care physicians were 56% less likely to record a diagnosis of depression during visits made by elderly patients, 37% less likely to do so during visits by African Americans, and 35% less likely to do so during visits by Medicaid patients. Visits with a depression diagnosis were, on average, 2.9 minutes longer in duration (16.4 vs 19.3) than visits without a depression diagnosis. Family practice and general practice physicians were 65% more likely to record a diagnosis of depression than internists. CONCLUSIONS: Many factors were associated with making and recording a depression diagnosis beyond the patient' reported symptoms. If rates of diagnosis are to improve, interventions that go beyond getting physicians to recognize the symptoms of depression are needed.

Amino acid substitution at position 99 affects the rate of CRP subunit exchange.

We investigated the characteristics of CRP having amino acid substitutions at position 99. Analysis of amino acid residue proximity to cAMP in molecular dynamics (MD) simulations of the CRP:(cAMP)(2) complex [García, A. E., and Harman, J. G. (1996) Protein Sci. 5, 62-71] showed repositioning of tyrosine 99 (Y99) to interact with the equatorial exocyclic oxygen atom of cAMP. To test the role of Y99 in cAMP-mediated CRP activation, Y99 was substituted with alanine (A) or phenylalanine (F). Cells that contained the WT or mutant forms of CRP induced beta-galactosidase in the presence of cAMP. Purified WT, Y99A, and Y99F CRP showed only a 3- to 4-fold difference in cAMP affinity. There were no apparent differences between the three forms of CRP in cAMP binding cooperativity, in CRP:(cAMP)(1) complex binding to lacP DNA, in the formation of CRP:cAMP:RNAP complexes at lacP, or in CRP efficacy in mediating lacP activity in vitro. The apo-form of Y99A CRP was more sensitive to protease than the apo-form of either WT CRP or Y99F CRP. Whereas the WT or Y99F CRP:(cAMP)(1) complexes were cleaved by protease at hinge-region peptide bonds, the Y99A CRP:(cAMP)(1) complex was cleaved at peptide bonds located at the subunit interface. The rates of subunit exchange for Y99A CRP, both in the apo-form and in a 1:1 complex with cAMP, were significantly greater than that measured for WT CRP. The results of this study show that tyrosine 99 contributes significant structural stability to the CRP dimer, specifically in stabilizing subunit association.

The role of nutritional therapy in the treatment of equine Cushing's syndrome and laminitis.

Equine Cushing's syndrome, a relatively common and complex condition, is difficult to treat with conventional medicine. Cushing's syndrome involves a hyperplasia or adenoma of the anterior pituitary gland. Biochemical alterations include increased endogenous cortisol, insulin resistance, elevated adrenocorticotrophic hormone, and decreased thyroid hormone levels. Symptoms include hirsutism with no loss of the winter coat in summer, refractory laminitis, weight problems (over- or underweight), polyuria/polydipsia (Pu/Pd), frequent infections, lowered immunity to intestinal parasites, decreased intestinal wall integrity, and infertility. Laminitis (an inflammation of the laminae of the foot) is a common and often fatal complication of Cushing's syndrome that tends to be refractory to conventional treatment. One of the most common therapies is phenylbutazone, a non-steroidal anti-inflammatory drug (NSAID) known to cause significant changes in the permeability of the intestinal wall. Recent research has shown an intestinal bacterial exotoxin to be one of the triggering factors in laminitis. By removing phenylbutazone and healing the intestinal wall, laminitis becomes more responsive to treatment. Good hoof-care combined with nutritional management and the application of other modalities, including acupuncture and Chinese and Western herbs, can complete the healing process. The successful treatment of equine Cushing's syndrome is one of the best examples of treating a disease using the holistic approach. While each case requires different combinations of modalities, the outcome is usually positive with individually selected treatments.

Pediatric length of stay guidelines and routine practice: the case of Milliman and Robertson.

BACKGROUND: Guidelines for inpatient length of stay (LOS) have been developed by Milliman and Robertson (M&R) and are widely applied by health plans. This study was designed to compare LOS for several pediatric conditions with the M&R LOS criteria using recent data and to determine if concordance of actual practice with M&R LOS criteria varied between children and adults. DESIGN: Administrative data from Pennsylvania hospitals from 1996 through 1998 were used to examine LOS for hospital discharges for 12 selected diagnoses for which M&R published guidelines for children and adults. PATIENTS: Discharge data for all patients discharged from public and private hospitals in Pennsylvania for which 1 of 12 selected diagnoses were examined. MAIN OUTCOME MEASURE: Length of stay. RESULTS: In Pennsylvania hospitals from 1996 through 1998, pediatric LOS was divergent for all conditions examined, although not to the extent found in a previous study examining data from New York State. Of note, median LOS for some conditions was shorter than M&R LOS criteria. The percentage of pediatric hospital discharges that exceeded the M&R LOS criteria ranged from 25% for pneumonia to 84% for meningitis. Adult hospital discharges exceeded M&R LOS criteria to a greater extent than did pediatric discharges for all conditions except for sickle cell crisis and meningitis. CONCLUSIONS: The M&R LOS criteria were divergent from routine practice for both children and adults. Greater divergence of adult discharges illustrates the need to consider comorbid conditions when implementing these guidelines. Thus, patient care may suffer if guidelines are implemented in an uninformed way. These findings emphasize the importance of using the best possible science when producing guidelines such as these.

Allosteric regulation of the cAMP receptor protein.

The cyclic AMP receptor protein (CRP) of Escherichia coli is a dimer made up of identical subunits. Each CRP subunit contains a cyclic nucleotide binding pocket and the CRP dimer exhibits negative cooperativity in binding cAMP. In solutions containing cAMP, CRP undergoes sequential conformation changes from the inactive apo-form through the active CRP:(cAMP)(1) complex to the less active CRP:(cAMP)(2) complex depending on the cAMP concentration. Apo-CRP binds DNA with low affinity and no apparent sequence specificity. The CRP:(cAMP)(1) complex exhibits high affinity, sequence-specific DNA binding and interacts with RNA polymerase, whether free in solution or complexed with DNA. The results of genetic, biochemical and biophysical studies have helped to uncover many of the details of cAMP-mediated allosteric control over CRP conformation and activity as a transcription factor. These studies indicate that cAMP binding produces only small, but significant, changes in CRP structure; changes that include subunit realignment and concerted motion of the secondary structure elements within the C-terminal DNA binding domain of each subunit. These adjustments promote CRP surface-patch interaction with RNA polymerase and protrusion of the F-helix to promote CRP site-specific interaction with DNA. Interactions between CRP and RNA polymerase at CRP-dependent promoters produce active ternary transcription complexes.

Physician gender and psychosocial care for children: attitudes, practice characteristics, identification, and treatment.

OBJECTIVE: To examine differences by physician gender in the identification and treatment of childhood psychosocial problems. DESIGN: Survey of patients (n = 19,963) and physicians (n = 366) in primary care offices in 2 large, practice-based research networks. Multivariate regressions were used to control for patient, physician, and visit characteristics, with a correction for the clustered sample. SUBJECTS: Children ages 4 to 15 years seen consecutively for nonemergent care. MEASURES: Physician report of attitudes, training, practice factors, and identification and treatment of psychosocial problems. Parental report of demographics and behavioral symptoms. RESULTS: Compared with male physicians, female physicians were less likely to view care for psychosocial problems as burdensome. They were more likely to see children who were female, younger, black or Hispanic, in single-parent households, enrolled in public or managed health plans, and with physical health limitations. Children seen by male physicians had higher symptom counts. Male physicians were more likely to report having primary care responsibility for their patient and that parents agree with their care plan. Female physicians spent more time with patients. After controlling for these differences, female physicians did not differ from male physicians in identification or treatment of childhood psychosocial problems. CONCLUSIONS: Male and female physicians see different kinds of children for different visit purposes and have different kinds of relationships with their patients. After controlling for these factors, management of childhood psychosocial problems does not differ by physician gender. Improving management of psychosocial conditions depends on identifying modifiable factors that affect diagnosis and treatment; our work suggests that characteristics of the practice environment, physician-patient relationship, and patient self-selection deserve more research.

Effect of breast surgery on serum levels of insulin-like growth factors (IGF-I, IGF-II, and IGF binding protein-3) in women with benign and malignant breast lesions.

BACKGROUND: There is evidence that insulin-like growth factors play a role in the development of breast cancer. Antiestrogens reduce circulating levels of IGF-I, but the influence of other breast cancer treatments, including surgery, is unknown and is investigated in this study. METHODS: Circulating serum concentrations of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured before and after breast surgery in 31 patients with breast cancer and 12 controls with benign breast lesions. Serum albumin was measured as a marker of the nonspecific metabolic effect of surgery. RESULTS: Serum IGF-I, IGF-II, IGFBP-3, and albumin fell 24 hours after surgery for breast cancer but largely normalized again over the next 7 days. The fall in IGF-I and IGFBP-3 was not significant when the change in serum albumin was used as a covariate, suggesting a nonspecific effect of surgery. However, the reduction in IGF-II remained significant when adjusted for albumin and was greater after lumpectomy of malignant tumors (-8 +/- 2%) compared with benign disease (2 +/- 2%, P = .001). The fall in IGF-II was significantly related to the size of the removed tumor. CONCLUSIONS: Breast cancer may directly influence the serum concentration of IGF-II, possibly by direct tumor production.

Interpreting results in mental health research.

It is often difficult to interpret the clinical or policy significance of findings from mental health research when results are presented only in terms of statistical significance. Results expressed in terms of p values or as a metric corresponding to a mental health status scale are seldom intuitively meaningful. To help interpret the significance of research results, we demonstrate a social validity approach that relates scores on mental health status scales to four subsequent major life events. A logistic regression model is used to estimate the relation between mental health status scores and the probability of subsequent major life events, using data obtained on Medicaid beneficiaries with schizophrenia from an evaluation of the Utah Prepaid Mental Health Plan. Using this relatively simple approach will demonstrate to policy makers, clinicians, and researchers the social impact of an outcome, thereby aiding in the interpretation of the significance of results.

Narrowing the gap in treatment of depression.

OBJECTIVE: Although effective treatments for depression exist, under or non-treatment of depression is common. Efforts were made in the early 1990s to improve recognition and treatment of depression, with many of those efforts targeted at groups most vulnerable to under-treatment. The purpose of this study is to assess treatment rates in 1993-1994 and 1996-1997. METHOD: Using nationally representative surveys of office-based practice covering the years 1993, 1994, 1996, and 1997, we obtained estimates of visits by adults in which depression was diagnosed and a prescription for antidepressant medication and/or psychotherapy was provided or ordered. RESULTS: The proportion of physician office visits in which a depression diagnosis was recorded did not change from 1993-1994 (3.48 percent) to 1996-1997 (3.40 percent). However, the rate of antidepressant prescription or psychotherapy rose from 74.2 percent of visits with a depression diagnosis in 1993-1994 to 82.3 percent of these visits in 1996-1997. Significantly lower rates of treatment for depression during office visits made by African American patients, elderly patients, and patients on Medicaid occurred in 1993-1994, but were not evident in 1996-1997, reflecting improved rates of depression treatment in these populations. CONCLUSIONS: Although rates of diagnosis of depression during office visits have not increased, treatment rates for depression are improving among those who are diagnosed, including groups of people who historically were less likely to be offered treatment. Additional efforts to improve recognition and diagnosis of depression in ambulatory medical practice and to improve dissemination of treatment are needed.

Informal carers of cancer patients: what are their unmet psychosocial needs?

This paper considers the significant unmet psychosocial needs of the informal carers of cancer patients, drawing on data generated in a 3-year UK study (1997-2000) on the psychosocial needs of cancer patients and their main carers. While the needs of the carers of cancer patients are increasingly being recognised in healthcare policy documents, there is relatively little published literature on these needs. A "significant unmet need" is defined here as a need deemed important by the carer, but which has not been met. A descriptive cross-sectional survey of carers was conducted and the responses of 195 carers relating to 48 psychosocial need items were analysed. A subset of these carers (n = 32) were interviewed. Forty-three per cent of carers had significant unmet needs. They were more likely to be those where the relationship to the patient was not that of a partner or spouse, more likely to have other caring responsibilities, and less likely to have friends or relations to call upon for help. Carers with unmet needs were also more likely to be in poor health themselves or to be caring for a patient who had reached the palliation-only phase in their cancer journey. The majority of carers expressed the importance of needs such as having good relationships with healthcare professionals and receiving honest information, but few expressed dissatisfaction with these aspects of need. Items of significant unmet need clustered around aspects of managing daily life, emotions, and also social identity for a sizeable minority of carers. These are the same areas of significant unmet need that concern patients. However, carers have more of these concerns, reflecting their comparative neglect. The paper also considers how these widespread concerns can be addressed.

The significant unmet needs of cancer patients: probing psychosocial concerns.

'Significant unmet needs' are those needs that patients identify as both important and unsatisfied. In this article we ask whether the overall needs of cancer patients are actually being met. We believe that the range of unmet need, and the kinds of patients who are more likely to claim unmet need, should be carefully identified. The needs responses of a series of 295 cancer patients in a cross-sectional survey were analysed. The majority expressed the opinion that information and good relationships with health care professionals were important, and few expressed dissatisfaction with these aspects of need. Similarly, needs items about support from family and friends were largely rated as important and satisfied. For a sizeable minority of patients, items of significant unmet need cluster around aspects of managing daily life, emotions, and social identity. The distribution of significant unmet needs is not random but is more likely to be experienced by patients who are younger, have a long-standing illness or disability, do not own/have use of a car, and/or have no religious faith. Furthermore, significant unmet needs relate to patients' ability to talk freely to a carer about the cancer, the degree to which the cancer interferes with social activities, and whether financial difficulties are experienced. Most of the significant unmet need is beyond the remit of services primarily designed for the treatment of disease. We consider whether multidisciplinary cancer teams can be expected to deal with all aspects of the cancer experience.

Mental health care utilization and expenditures by children in foster care.

OBJECTIVE: To determine the percentage of children with mental health diagnoses and utilization and expenditures of mental health services among children in foster care compared with other children receiving Medicaid, including those with disabilities. DESIGN: Analysis of Medicaid claim and eligibility records in southwestern Pennsylvania for fiscal year 1995. POPULATION: A total of 39,500 children between ages 5 and 17 years continuously eligible for Medicaid in southwestern Pennsylvania were included in the analysis. MAIN OUTCOME MEASURES: Percentage of children with mental health diagnoses and mental and general health care utilization and expenditures classified by participation in foster care and Medicaid eligibility. RESULTS: Children in foster care were 3 to 10 times more likely to receive a mental health diagnosis, had 6.5 times more mental health claims, were 7.5 times more likely to be hospitalized for a mental health condition, and had mental health expenditures that were 11.5 times greater ($2082 vs $181) than children in the Aid to Families With Dependent Children (AFDC) program. Overall, utilization rates, expenditures, and prevalence of psychiatric conditions for children in foster care were comparable with those of children with disabilities. CONCLUSIONS: Children in foster care are significantly more likely to suffer from mental health conditions and use more mental health and general health services than AFDC children. Service use and expenditures are comparable with those of disabled children, suggesting that reimbursement rates and care management for children in foster care need to be reexamined.